Clinical Trials Register

Summary
EudraCT Number:	2007-002693-66
Sponsor's Protocol Code Number:	0822-018
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-02-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Bulgarian Drug Agency

A.2

EudraCT number

2007-002693-66

A.3

Full title of the trial

An Open-Label 5 Years-2nd Extension to:
A phase III Randomized, Placebo-Controlled Clinical Trial to Assess the Safety and Efficacy of
Odanacatib (MK-0822) to Reduce the Risk of Fracture in Osteoporotic Postmenopausal
Women Treated With Vitamin D and Calcium

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

N/A

A.4.1

Sponsor's protocol code number

0822-018

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharpe & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Sharpe & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Clinical Monitor
B.5.3	Address:
B.5.3.1	Street Address	126 East Lincoln Avenue, P.O.Box 2000
B.5.3.2	Town/ city	Rahway
B.5.3.3	Post code	NJ 07065-0900
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 732594 4136
B.5.5	Fax number	+1732594 4450
B.5.6	E-mail	antonio_lombardi@merck.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Odanacatib
D.3.2	Product code	MK-0822
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	odanacatib
D.3.9.1	CAS number	603139-19-1
D.3.9.2	Current sponsor code	MK-0822
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vitamin D3, Cholecalciferol
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	cholecalciferol
D.3.9.1	CAS number	67-97-0
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2800
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Postmenopausal Osteoporosis

E.1.1.1

Medical condition in easily understood language

N/A

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10031285
E.1.2	Term	Osteoporosis postmenopausal
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Second extension
(1) To assess change from baseline in total hip BMD after 10 years of treatment.
(2) To assess safety and tolerability of long-term treatment.

E.2.2

Secondary objectives of the trial

Second extension
- To assess change from baseline (randomization into base period) in BMD of lumbar spine, femoral neck, and trochanter.
- To determine the incidence of morphometrically assessed vertebral fractures.
- To determine the incidence of all clinical (both non-vertebral and vertebral) fractures.
- To assess changes from baseline (start of open-laber treatment) in BMD of lumbar spine, total hip, femoral neck, and trochanter during 5 years of treatment with odanacatib 50 mg once- weekly.
- To determine the incidence of morphometrically assessed vertebral fractures during 5 years of treatment with odanacatib 50 mg once-weekly.
- To determine the incidence of all clinical (both non-vertebral and vertebral) fractures during 5 years of treatment with odanacatib 50 mg once-weekly.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Second extension

In order to be eligible for participation in this trial, the subject must:

NOTE: Subjects inappropriately randomized into the trial (i.e., those who do not meet entry criteria) may be discontinued from the study at the discretion of the Sponsor.

1. Have met all initial inclusion criteria and ha ve not met any of the exclusion or discontinuation criteria of either the base or 1st extension studies.

NOTE: There is no specific BMD T-score required for eligibility in this extension study. If a subject has met excessive bone loss criteria at her end of study visit for the
1st extension study, or the 2nd extension screening visit, she can continue into this 2nd extension.
2. Be an active participant and have successfully completed the 1st extension study on study medication. (An interruption of approximately 12 weeks from the end of the first extension study to the begining of 2nd extension study is permissible).

3. Be assessed by the investigator as having had appropirate compliance during the base and 1st extension studies.

4. Have at least one hip (e.g. contains no hardware from or thopedic procedures) AND
suitable spinal anatomy that is evaluable by DXA.

5. Understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agree to participate by providing informed consent.

6. Be able to read, understand and complete questionnaires and diaries. NOTE: If a subject who understands the purpose and use of the diary
cards and study questionnaires is unable to complete these without assistance (e.g. due to visual problems, difficulty writing due to arthritis,

inability to read, etc.), a family member or care-giver may assist or may complete the diary card on her behalf

7. Be in generally good health, based on medical history, physical examination, and laboratory evaluation.

E.4

Principal exclusion criteria

Second extension:

The subject must be excluded from participating in the trial if the subject:

1. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the bes t interest of the subject to participate.

2. Is receiving treatment as follows:

1) Current use of osteoporosis therapy including: bisphosphonates, PTH, strontium, systemic estrogen + progestin, raloxifene or other SERM, RANK ligand inhibitor, or sub-cutaneous calcitonin. (Note: use of intranasal calcitonin is permitted.)

2) Subject is planning to initiate or is currently using long-term therapy (6 weeks or longer) with any CYP3A4 inducers (see Appendix 12.5 for examples).

3. Is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be obtained or the subject cannot read or comprehend the written material.

4. Has participated in an investigational drug study other than the base study or 1st
extension study within the past 30 days.

5. Is currently a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.

E.5 End points

E.5.1

Primary end point(s)

Base study
Morphometric fractures, hip fractures, and clinical non-vertebral fractures.

Extension
The primary focus of this study will be on morphometic vertebral fractures. Lateral thoracic and lumbar spine radiographs will be obtained for each patient at baseline of the core study, Month 6, Month 12, and yearly thereafter until the end of the 5-year doubleblind extension study. The primary endpoint will be the first morphometrically assessed vertebral fracture per patient determined from these radiographs, analyzed as intervalcensored
survival data. All available x-ray data will be included in the analyses and time windows will be defined in a separate document to define timing, extending those of the core study.

Second extension:

For subjects with an allocation number ending in an odd number BMD will be measured at the hip and lumbar spine at screening, Month 72, Month 96, Month 120, Month 144 and end of study visits. For subjects with an allocation number ending in an even number BMD will be measured by DXA at the hip and lumbar spine at screening, Month 84, Month 108, Month 132 and end of study visits. DXA of the distal forearm and total body will still be performed for those subjects that had this measurement performed as part of their randomization visit in the base study when their BMD of the hip and lumbar spine are assessed. The primary endpoint of this extension study is the percent change from baseline in total hip BMD, in subjects originally randomized to a Odanacatib in the base study.

For the hip BMD measurement, the side of the hip measured must be consistent throughout the study. In case a change in hip side occurred in the base study, the change from the start of open-label treatment will be

calculated on the available hip side. If the hip side that is being measured becomes fractured during the study, then data of that hip side will be excluded from the time of the fracture onward.

E.5.1.1

Timepoint(s) of evaluation of this end point

N/A

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

143

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS at latest June 2020

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

5000

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

4000

F.4.2.2

In the whole clinical trial

5000

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-01-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-01-22

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-02-01

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